Evaluation of Typhoid Conjugate Vaccine Effectiveness in Ghana (TyVEGHA)

A Cluster-randomised Controlled Phase IV Trial Assessing the Impact of a Vi-Polysaccharide Conjugate Vaccine in Preventing Typhoid Infection in Asante Akim, Ghana (TyVEGHA)

A cluster-randomised controlled Phase IV trial (cRCT) assessing the impact of a Vi-Polysaccharide conjugate vaccine in preventing typhoid infection in Asante Akim, Ghana (TyVEGHA) with a primary endpoint of determining the total protection conferred by single-dose vaccination with Vi-TT against blood culture-confirmed symptomatic S. Typhi infection in the intervention vaccine clusters, compared with the control vaccine clusters.

Study Overview

• Status: Recruiting
• Conditions: Typhoid Fever
• Intervention / Treatment: Biological: Vi-TT; Biological: MCV-A vaccine

Detailed Description

Typhoid fever remains a significant health problem in sub-Saharan Africa, with incidence rates >100 cases per 100,000 person-years of observation. Despite the prequalification of safe and effective typhoid conjugate vaccines (TCV), the uptake of these vaccines in African countries has remained low. Real-life effectiveness data, which inform public health programs on the impact of TCVs in reducing typhoid-related mortality and morbidity, are critical to enhancing the introduction of TCVs in high-burden settings. Here we describe a cluster-randomized trial to investigate population-level protection of TCV against blood culture-confirmed typhoid fever. A total of 80 geographically distinct clusters have been delineated within the Agogo district of the Asante Akim region in Ghana. Clusters will be randomized to the intervention arm receiving TCV or a control arm receiving the meningococcal A conjugate vaccine. The primary study endpoint is the overall protection of TCV against blood culture-confirmed typhoid fever. Total, direct, and indirect protection will be measured as secondary outcomes. Blood culture-based enhanced surveillance will enable the estimation of incidence rates in the intervention and control clusters. Evaluation of the real-world impact of TCVs will improve uptake of prequalified/licensed safe and effective typhoid vaccines in public health programs of high burden settings.

• Study Type: Interventional
• Enrollment (Estimated): 23000
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Birkneh T Tadesse, PhD; Phone Number: +821098041348; Email: birkneh.tadesse@ivi.int
• Study Contact Backup: Name: Thaint Thaint Thwe, MBBS, MSc.; Phone Number: +821037907535; Email: ThaintThaint.Thwe@ivi.int

Study Locations

• Ghana
  • Ashanti
    • Kumasi, Ashanti, Ghana, PMB
      • Recruiting
      • Kwame Nkrumah University of Science and Technology
      • Contact: Ellis Owusu Dabo, PhD; Phone Number: +233201964425; Email: owusudabo@yahoo.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 2 years to 11 years (Child)
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria: In order to be eligible to participate in this study, an individual must meet the following criteria:

• Healthy participants aged 9 months to <16 years (i.e., ≤15 years and 364 days) of age at the time of vaccination
• Participants/Parents/legally authorized representative (LAR) who have voluntarily given informed assent (sought from participants aged 12 years to <16 years) and informed consent
• Participants/Parents/LAR living within study target area at the time of vaccination and willing to follow the study procedures and be available for the entire duration of the study

Exclusion Criteria: An individual who meets any of the following criteria will be excluded from participation in this study:

• Known allergy to any vaccine component
• Self-reported ongoing acute and/or chronic illness
• Any self-reported coagulopathies
• Any medical or social compelling reasons in the judgment of a clinical physician
• Self-reported pregnancy/Positive urine pregnancy test or lactating
• Previous typhoid vaccination in the last 5 years (proven by the presentation of a vaccine card or self-reporting).

Temporary exclusion criteria

• Self-reported fever (elevated tympanic (≥38°C) or axillary temperature (≥37.5°C)) within 24 hours of vaccination
• Self-reported use of antipyretics within 4hours prior to vaccination
• Any other vaccination during the last 4 weeks (proven by the presentation of a vaccine card or self-reporting)
• Girls ≥11 years of age with self-reported irregular menstruation or who do not know their last menstruation date

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Vi-TT Arm; A single dose of Vi-TT to children 9 months to 15 years of age.	Biological: Vi-TT; Single-dose V-TT administered to children and adolescents between the ages of 9 months to 15 years.
Active Comparator: MCV-A arm; A single dose of MCV-A vaccine to the comparator group.	Biological: MCV-A vaccine; Single-dose of MCV-A vaccine (a meningococcal vaccine)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Total Protection	The incidence of blood culture-confirmed symptomatic TF in all vaccine recipients of the intervention clusters, compared with control clusters.	3 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Safety Assessment	1) Proportion of adverse events in participants receiving Vi-TT compared with MCV-A, measured by: The proportion of participants in each group of a sub-sample of the cohort developing adverse events/adverse reactions within the first 7 days post-vaccination.; The proportion of participants in each group of the cohort developing serious adverse events during the entire study period, as determined by self-reporting at follow-up contact.	3 years
Overall protection	The incidence of blood culture-confirmed symptomatic TF in all residents of the intervention clusters compared with that in all residents of control clusters	3 years
Total protection against severe typhoid.	The incidence of severe TF in vaccinated individuals in intervention clusters compared to control clusters	3 years
Total protection against clinical typhoid.	The incidence of clinical typhoid fever cases, defined as persistent fever (tympanic (≥38.0℃) or axillary temperature (≥37.5℃) or reported fever for ≥3 consecutive days) with abdominal complaints at a study surveillance site in vaccinated individuals in intervention clusters compared to control clusters.	3 years
Overall protection against clinical typhoid.	The incidence of clinical typhoid fever cases presenting at a study surveillance site among all residents of the Vi-TT clusters compared to the control vaccine clusters.	3 years
Indirect Protection aganist Blood Culture Confirmed Typhoid.	The incidence of blood culture-confirmed symptomatic TF in non-vaccinees of the intervention clusters compared with control clusters.	3 years
Seroconversion rates	The seroconversion rates as measured by enzyme linked immunosorbent assay (anti-Vi IgM and IgG) for S. Typhi and iNTS at defined time points in a age-stratified subset of intervention and control vaccinees.	3 years
Geometric mean titers	The antibody concentration as measured by enzyme linked immunosorbent assay (anti-Vi IgM and IgG) for S. Typhi and iNTS at defined time points in a age-stratified subset of intervention and control vaccinees.	3 years

Collaborators and Investigators

• Sponsor: International Vaccine Institute
• Collaborators: University of Maryland, Baltimore; International Centre for Diarrhoeal Disease Research, Bangladesh; University of Cambridge; Kwame Nkrumah University of Science and Technology; Fondation Mérieux
• Investigators: Principal Investigator: Florian Marks, PhD, University of Cambridge; Principal Investigator: Ellis Owusu Dabo, PhD, Kwame Nkrumah University of Science and Technology

Study record dates

Study Major Dates

• Study Start (Actual): August 24, 2021
• Primary Completion (Estimated): December 31, 2024
• Study Completion (Estimated): December 31, 2024

Study Registration Dates

• First Submitted: March 17, 2021
• First Submitted That Met QC Criteria: April 15, 2021
• First Posted (Actual): April 21, 2021

Study Record Updates

• Last Update Posted (Actual): March 8, 2024
• Last Update Submitted That Met QC Criteria: March 6, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Keywords: Typhoid; Typhoid conjugate vaccine; Cluster randomised trial
• Additional Relevant MeSH Terms: Infections; Gram-Negative Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Enterobacteriaceae Infections; Salmonella Infections; Typhoid Fever
• Other Study ID Numbers: TyVEGHA2020

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: Sharing can be considered on a case-by-case basis considering the intended use and impact.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No